Urology Commons^™

Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti

Dissertations and Theses (Open Access)

After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but …

Safety Of Hexaminolevulinate For Blue Light Cystoscopy In Bladder Cancer. A Combined Analysis Of The Trials Used For Registration And Postmarketing Data., J Alfred Witjes, Leonard G. Gomella, Arnulf Stenzl, Sam S. Chang, Dirk Zaak, H Barton Grossman

Department of Urology Faculty Papers

OBJECTIVE: To detail and put into perspective, safety of hexaminolevulinate blue light cystoscopy (HAL-BLC), including repeated use, based on combined data of controlled trials used for registration of HAL and postmarketing experience.

METHODS: Safety data of 2 randomized comparative studies (group 1) and 4 within patient control studies (group 2) were combined. Postmarketing data from >200,000 patients were analyzed.

RESULTS: In group 1, 533 patients were examined with HAL-BLC and 499 with white light (WL) cystoscopy. In group 2, 791 patients were examined with both WL and HAL-BLC. Between 73% and 93% of these patients had concomitant diseases. Between 41% …

Hiv-1 Subtype A Gag Variability And Epitope Evolution, Syed Hani Abidi, Marcia L. Kalish, Farhat Abbas, Sarah Rowland-Jones, Syed Ali

Section of Urology

Objective: The aim of this study was to examine the course of time-dependent evolution of HIV-1 subtype A on a global level, especially with respect to the dynamics of immunogenic HIV gag epitopes.
Methods: We used a total of 1,893 HIV-1 subtype A gag sequences representing a timeline from 1985 through 2010, and 19 different countries in Africa, Europe and Asia. The phylogenetic relationship of subtype A gag and its epidemic dynamics was analysed through a Maximum Likelihood tree and Bayesian Skyline plot, genomic variability was measured in terms of G → A substitutions and Shannon entropy, and the time-dependent …

Surgical Management Of Pheochromocytoma In A 13-Week Pregnant Woman, Mazhar Ali Memon, Wajahat Aziz, Farhat Abbas

Section of Urology

A 34-year-old 13-week pregnant woman presented with hypertension refractory to medical therapy and on workup was found to have a right adrenal mass. Due to her persistent increased blood pressure she was advised urinary vanillylmandelic acid (VMA) and its level was raised. MRI of the abdomen showed a well-circumcised lesion in the right adrenal of 3.0×2.5 cm suggestive of pheochromocytoma. The patient was started on antihypertensives including α-blockers and β-blockers and planned for right open adrenalectomy. Intraoperatively, blood pressure was raised up to 180/110 mm Hg on slight manipulation of adrenal gland which was controlled with glyceryl-trinitrate and volatile agents. …

Prostate Cancer: Alcohol, Cancer And 5Α-Reductase Inhibitors-Is There A Link?, Leonard G Gomella

Department of Urology Faculty Papers

Two major trials have been performed to determine the effect of 5α-reductase inhibitors on subsequent diagnoses of prostate cancer. Both trials showed that high alcohol intake significantly increased prostate cancer risk among men allocated to the treatment arms. The recommendation that patients eliminate alcohol when taking 5α-reductase inhibitors seems appropriate.

Promoter Hypermethylation Of Tumor Suppressor Genes Correlates With Tumor Grade And Invasiveness In Patients With Urothelial Bladder Cancer, Shumaila M. Bilgrami, Sohail A. Qureshi, Shahid Pervez, Farhat Abbas

Section of Urology

Purpose: To investigate the promoter methylation status at selected loci which encode for key proteins involved in apoptosis, DNA repair, cell cycle control and progression in urothelial cell carcinoma of bladder and compare the findings from tissue samples with that of plasma.
Methods: Total genomic DNA was isolated from 43 non-muscle invasive (low grade) and 33 muscle invasive (high grade) urothelial bladder cancer samples along with 10 control cases of normal bladder mucosa. Promoter methylation status was investigated for RASSF1A, APC, MGMT, CDKN2A and CDKN2B genes using real-time methylation-specific PCR with SYBR® green. Plasma samples from 16 patients with muscle …

Preoperative And Operative Factors Associated With Complications Following Radical Nephroureterectomy, A. Arnouk, C. Lallas, E. Trabulsi, J. Raman

Sigma Xi Student Research Day

Abstract

Radical nephroureterectomy (RNU) is the gold standard for managing upper-tract urothelial carcinoma. We review preoperative, operative, and pathologic characteristics of patients undergoing RNU to identify factors associated with perioperative complications. A retrospective review of institutional databases from 8 academic centers identified 732 patients who underwent RNU. Data on preoperative, operative, and pathologic indices were collected. Almost 40% of patients in our cohort experienced a complication within 30 days of RNU. Increasing age, higher Charlson score, and lower baseline renal function were independently associated with patients developing complications. Longer OR duration and intraoperative transfusion requirement were also associated with post-RNU …

Promoter Hypermethylation Of Tumor Suppressor Genes Correlates With Tumor Grade And Invasiveness In Patients With Urothelial Bladder Cancer, Shumaila M. Bilgrami, Sohail A. Qureshi, Shahid Pervez, Farhat Abbas

Department of Pathology and Laboratory Medicine

Purpose: To investigate the promoter methylation status at selected loci which encode for key proteins involved in apoptosis, DNA repair, cell cycle control and progression in urothelial cell carcinoma of bladder and compare the findings from tissue samples with that of plasma.
Methods: Total genomic DNA was isolated from 43 non-muscle invasive (low grade) and 33 muscle invasive (high grade) urothelial bladder cancer samples along with 10 control cases of normal bladder mucosa. Promoter methylation status was investigated for RASSF1A, APC, MGMT, CDKN2A and CDKN2B genes using real-time methylation-specific PCR with SYBR® green. Plasma samples from 16 patients with muscle …

Metformin Inhibits Androgen-Induced Igf-Ir Up-Regulation In Prostate Cancer Cells By Disrupting Membrane-Initiated Androgen Signaling., Roberta Malaguarnera, Antonella Sacco, Alaide Morcavallo, Sebastiano Squatrito, Antimo Migliaccio, Andrea Morrione, Marcello Maggiolini, Antonino Belfiore

Department of Urology Faculty Papers

We have previously demonstrated that, in prostate cancer cells, androgens up-regulate IGF-I receptor (IGF-IR) by inducing cAMP-response element-binding protein (CREB) activation and CREB-dependent IGF-IR gene transcription through androgen receptor (AR)-dependent membrane-initiated effects. This IGF-IR up-regulation is not blocked by classical antiandrogens and sensitizes cells to IGF-I-induced biological effects. Metformin exerts complex antitumoral functions in various models and may inhibit CREB activation in hepatocytes. We, therefore, evaluated whether metformin may affect androgen-dependent IGF-IR up-regulation. In the AR(+) LNCaP prostate cancer cells, we found that metformin inhibits androgen-induced CRE activity and IGF-IR gene transcription. CRE activity requires the formation of a CREB-CREB …

Do Not Judge A Kidney By Its Pelvis: A Rare Case Of An Unobstructed Dilated Renal Pelvis, Aaron D. Martin, Craig A. Peters

Urology Faculty Publications

We present a rare case of an unobstructed dilated renal pelvis in a newborn female. Prenatal imaging documented a large abdominal cyst in a stable fetus. Postnatal imaging confirmed persistence of this large cyst but with an unclear etiology. The child was taken to surgery by the pediatric surgeons with concern for a possible harmful nonurologic diagnosis. Intraoperative findings were that of a severely dilated renal pelvis; however, in the absence of an expected ureteropelvic junction obstruction. Reduction pyeloplasty without interference of the ureteropelvic junction proved successful.

Training The Resident In Percutaneous Nephrolithotomy, Muhammad Hammad Ather, Chi-Fai Ng, Gholamraza Pourmand, Palle J. Osther

Section of Urology

Objective: From the trainers' perspective percutaneous nephrolithotomy (PCNL) is one of the most challenging endourological procedures. In this review we examine the problems arising when training residents in PCNL, and how to facilitate this process.
Methods: The recommendations are derived from discussions and consensus during the First European Urolithiasis Society (EULIS) meeting held in London in September 2011. In addition, we searched Medline for articles identified using the keywords 'training', 'percutaneous surgery', 'renal calculi', 'PCNL', 'virtual reality' and 'simulators'. We also assessed the effect of modern technology, including the availability of virtual reality models vs. operating room training, and how …

Urology Training In The Developing World: The Trainers' Perspective, M Hammad Ather, Tahmeena Siddiqui

Section of Urology

Context: Despite producing some of the leading urologists in the world, urological training in the developing world is marred by inconsistency, and a lack of structure and focus on evidence-based practice. In this review we address these issues from the trainers' perspective.
Introduction: Teaching the art and science of urological practice is a demanding task. It not only involves helping the resident to develop the depth of cognitive knowledge, but also to have an appropriate surgical judgement, and an ability to act quickly but thoughtfully and, when necessary, decisively.
Discussion: The surgeon must have compassion, communication skills, be perceptive and …

Systematic Analysis Of A Xenograft Mice Model For Kshv+ Primary Effusion Lymphoma (Pel), Lu Dai, Jimena Trillo-Tinoco, Lihua Bai, Baoli Kang, Zengguang Xu, Xiaofei Wen, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), which arises preferentially in the setting of infection with human immunodeficiency virus (HIV). Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+) PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells …

The Role Of Magnetic Resonance Imaging (Mri) In Focal Therapy For Prostate Cancer: Recommendations From A Consensus Panel, B. G. Muller, J. J. Futterer, R. T. Gupta, A. Katz, A. Kirkham, J. Kurhanewicz, J. W. Moul, A. R. Rastinehad, C. Robertson, M. Marberger, +7 Additional Authors

Journal Articles

OBJECTIVE: To establish a consensus on the utility of multiparametric magnetic resonance imaging (mpMRI) to identify patients for focal therapy. METHODS: Urological surgeons, radiologists, and basic researchers, from Europe and North America participated in a consensus meeting about the use of mpMRI in focal therapy of prostate cancer. The consensus process was face-to-face and specific clinical issues were raised and discussed with agreement sought when possible. All participants are listed among the authors. Topics specifically did not include staging of prostate cancer, but rather identifying the optimal requirements for performing MRI, and the current status of optimally performed mpMRI to …

A Systematic Review And Meta-Analysis Of Tobacco Use And Prostate Cancer Mortality And Incidence In Prospective Cohort Studies, F. Islami, D. M. Moreira, P. Boffetta, S. J. Freedland

Journal Articles

Context: An association between tobacco smoking and prostate cancer (PCa) incidence and mortality was suggested in an earlier meta-analysis of 24 prospective studies in which dose-response associations and risks per unit of tobacco use were not examined. Objective: We investigated the association between several measures of tobacco use and PCa mortality (primary outcome) and incidence (secondary outcome) including dose-response association. Evidence acquisition: Relevant articles from prospective studies were identified by searching the PubMed and Web of Science databases (through January 21, 2014) and reference lists of relevant articles. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using …

Health-Related Quality Of Life (Hrqol) In Cystine Compared With Non-Cystine Stone Formers, F. Modersitzki, L. Pizzi, M. Grasso, D. S. Goldfarb

Journal Articles

Cystinuria is a genetic cause of recurrent kidney stones which may be more recurrent and larger than more common non-cystine stones. They may have a greater impact on health-related quality of life (HRQoL). We measured this impact by surveying HRQoL in patients with stones, comparing non-cystine stone formers (NCSF) to cystine stone formers (CYSF) and both groups to normative values of the US population. We used SF-36v2 via an internet instrument. CYSF patients were recruited via cystinuria-related websites, two patient advocacy groups, and an active endourology practice. NCSF patients were recruited from the same practice and by email. Total n …

Cigarette Smoking Is Associated With An Increased Risk Of Biochemical Disease Recurrence, Metastasis, Castration-Resistant Prostate Cancer, And Mortality After Radical Prostatectomy: Results From The Search Database, D. M. Moreira, W. J. Aronson, M. K. Terris, C. J. Kane, C. L. Amling, M. R. Cooperberg, P. Boffetta, S. J. Freedland

Journal Articles

BACKGROUND: The current study was conducted to analyze the association between cigarette smoking and metastasis (the primary outcome) as well as time to biochemical disease recurrence (BCR), metastasis, castration-resistant prostate cancer (CRPC), and prostate cancer-specific and overall mortality (secondary outcomes) after radical prostatectomy among men from the Shared Equal Access Regional Cancer Hospital cohort. METHODS: A retrospective analysis was performed of 1450 subjects for whom smoking status was available from preoperative notes. Analysis of baseline characteristics by smoking status was performed using the chi-square and rank sum tests. The association between smoking status and time to the event was analyzed …

Predicting Bone Scan Positivity After Biochemical Recurrence Following Radical Prostatectomy In Both Hormone-Naive Men And Patients Receiving Androgen-Deprivation Therapy: Results From The Search Database, D. M. Moreira, M. R. Cooperberg, L. E. Howard, W. J. Aronson, C. J. Kane, M. K. Terris, C. L. Amling, M. Kuchibhatla, S. J. Freedland

Journal Articles

BACKGROUND: To evaluate the factors associated with positive bone scans after biochemical recurrence (BCR) following radical prostatectomy in both hormone-naive subjects and subjects after androgen-deprivation therapy (ADT). METHODS: Retrospective analysis of 380 bone scans of 301 hormone-naive subjects and 214 bone scans of 137 subjects after ADT following BCR from the Shared Equal Access Regional Cancer Hospital database. Generalized estimating equations and local regression plots were used to evaluate bone scan positivity by patients' demographics, pathological features, PSA levels and kinetics. RESULTS: Among hormone-naive subjects and subjects on ADT, bone scan positivity was seen in 24 (6%) and 65 (30%) …

Pharmacologically Induced Erect Penile Length And Stretched Penile Lengh Are Both Good Predictors Of Post-Inflatable Prosthesis Penile Length, E. C. Osterberg, A. Maganty, R. Ramasamy, J. F. Eid

Journal Articles

Inflatable penile prosthesis (IPP) remains the gold standard for the surgical treatment of refractory erectile dysfunction; however, current literature to aid surgeons on how best to counsel patients on their postoperative inflated penile length is lacking. The aim of this study was to identify preoperative parameters that could better predict postoperative penile length following insertion of an IPP. Twenty men were enrolled in a prospective study examining penile lengths before and after IPP surgery. Patients with Peyronie's disease were excluded from this analysis. Baseline preoperative characteristics, including body mass index, history of hypertension, diabetes, Sexual Health Inventory for Men scores …

Robotic Assisted Laparoscopic Prostatectomy In Men With Proctocolectomy And Restorative Ileal Pouch-Anal Anastomosis, M. Leapman, Y. S. Kwon, S. A. Collingwood, E. Chin, M. Katsigeorgis, A. R. Hobbs, D. B. Samadi

Journal Articles

We conducted a retrospective chart review of robotic prostatectomies done by a single surgeon between 2003 and 2012. During that time period, we identified two patients within the year 2012, with ileal pouch-anal anastomosis (IPPA) who also underwent robotic prostatectomies. The demographics and postoperative characteristics of the two patients were assessed. In both patients, prostatectomy, bilateral nerve sparing, and pelvic lymphadenectomy were successfully performed and the integrity of ileal pouch was maintained. There was a mean surgical time of 144.5 minutes, and an average estimated blood loss was 125 mL. Both patients were discharged on the second day postoperatively. In …